Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs

Association between anemia and household water source or sanitation in preschool children: the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

BackgroundThe associations between anemia and household water source and sanitation remain unclear.ObjectivesWe aimed to assess the associations between anemia and household water source or sanitation in preschool children (PSC; age 6-59 mo) using population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.MethodsWe analyzed national and subnational data from 21 surveys, representing 19 countries (n = 35,963). Observations with hemoglobin (Hb) and ≥1 variable reflecting household water source or sanitation were included. Anemia was defined as an altitude-adjusted Hb concentration <110 g/L. Household water source and sanitation variables were dichotomized as "improved" or "unimproved." Poisson regressions with robust variance estimates were conducted for each survey, adjusting for child sex, age, household socioeconomic status, maternal education, and type of residence.ResultsAccess to an improved water source and improved sanitation ranged from 29.9% (Burkina Faso) to 98.4% (Bangladesh, 2012), and from 0.2% (Kenya, 2007) to 97.4% (Philippines), respectively. Prevalence of anemia ranged from 20.1% (Nicaragua) to 83.5% (Bangladesh, 2010). Seven surveys showed negative associations between anemia and improved sanitation. Three surveys showed association between anemia and improved water, with mixed directions. Meta-analyses suggested a protective association between improved household sanitation and anemia [adjusted prevalence ratio (aPR) = 0.88; 95% CI: 0.79, 0.98], and no association between improved household water and anemia (aPR = 1.00; 95% CI: 0.91, 1.10). There was heterogeneity across surveys for sanitation (P < 0.01; I2 = 66.3%) and water (P < 0.01; I2 = 55.8%).ConclusionsAlthough improved household sanitation was associated with reduced anemia prevalence in PSC in some surveys, this association was not consistent. Access to an improved water source in general had no association with anemia across surveys. Additional research could help clarify the heterogeneity between these conditions across countries to inform anemia reduction programs

Intraindividual double burden of overweight and micronutrient deficiencies or anemia among preschool children

Background: Child overweight prevalence is increasing globally, but micronutrient deficiencies persist. Objectives: We aimed to 1) describe the prevalence and distribution of intraindividual double burden of malnutrition (DBM), defined as coexistence of overweight or obesity (OWOB) and either micronutrient deficiencies or anemia, among preschool children; 2) assess the independence of DBM components, e.g., whether the prevalence of DBM is greater than what would be expected by chance; and 3) identify predictors of intraindividual DBM, to guide intervention targeting. Methods: We analyzed data from 24 population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (separately by survey; n = 226 to n = 7166). We defined intraindividual DBM as coexisting OWOB and ≥1 micronutrient deficiency [e.g., Micronutrient Deficiency Index (MDI) \u3e 0; DBM-MDI] or anemia (DBM-Anemia). We assessed independence of DBM components with the Rao–Scott chi-square test and examined predictors of DBM and its components with logistic regression. Results: DBM prevalence ranged from 0% to 9.7% (median: 2.5%, DBM-MDI; 1.4%, DBM-Anemia), reflecting a lower prevalence of OWOB (range: 0%–19.5%) than of micronutrient deficiencies and anemia, which exceeded 20% in most surveys. OWOB was generally not significantly associated with micronutrient deficiencies or anemia. In more than half of surveys, children 6–23 mo of age, compared with ≥24 mo, had greater adjusted odds of DBM-Anemia, anemia, and micronutrient deficiencies. Child sex and household socioeconomic status, urban location, and caregiver education did not consistently predict DBM or its components. Conclusions: Intraindividual DBM among preschool children was low but might increase as child OWOB increases. The analysis does not support the hypothesis that DBM components cluster within individuals, suggesting that population-level DBM may be addressed by programs to reduce DBM components without targeting individuals with DBM

Malaria infection confounds inflammation-adjusted micronutrient biomarker concentrations in children and women in Malawi: a secondary analysis of the 2015/2016 Malawi micronutrient survey

Inflammation and infections such as malaria affect concentrations of many micronutrient biomarkers and hence estimates of nutritional status. We aimed to assess the relationship between malaria infection and micronutrient biomarker concentrations in pre-school children (PSC), school-age children (SAC) and women of reproductive age (WRA) in Malawi and examine the potential role of malarial immunity on the relationship between malaria and micronutrient biomarkers. Data from the 2015/2016 Malawi micronutrient survey were used. The associations between current or recent malaria infection, detected by rapid diagnostic test and concentration of serum ferritin, soluble transferrin receptor (sTfR), zinc, serum folate, red blood cell folate and vitamin B12 were estimated using multivariable linear regression. Factors related to malarial immunity including age, altitude and presence of hemoglobinopathies were examined as effect modifiers. Serum ferritin, sTfR and zinc were adjusted for inflammation using the BRINDA method. Malaria infection was associated with 68 % (95 % CI 51, 86), 28 % (18, 40) and 34 % (13, 45) greater inflammation-adjusted ferritin in PSC, SAC and WRA, respectively (P < 0·001 for each). In PSC, the positive association was stronger in younger children, high altitude and children who were not carriers of the sickle cell trait. In PSC and SAC, sTfR was elevated (+ 25 % (16, 29) and + 15 % (9, 22) respectively, P < 0·001). Serum folate and erythrocyte folate were elevated in WRA with malaria (+ 18 % (3, 35) and + 11 % (1, 23), P = 0·01 and P = 0·003 respectively). Malaria affects the interpretation of micronutrient biomarker concentrations, and examining factors related to malarial immunity may be informative

Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation

Urine selenium concentration is a useful biomarker for assessing population level selenium status

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys

Spatial analysis of urine zinc (Zn) concentration for women of reproductive age and school age children in Malawi

Zinc (Zn) is an essential micronutrient, and Zn deficiency remains a major global public health challenge. Recognised biomarkers of population Zn status include blood plasma or serum Zn concentration and proxy data such as dietary Zn intake and prevalence of stunting. Urine Zn concentration is rarely used to assess population Zn status. This study assessed the value of urine Zn concentration as a biomarker of population Zn status using a nationally representative sample of non-pregnant women of reproductive age (WRA) and school-aged children (SAC) in Malawi. Spot (casual) urine samples were collected from 741 WRA and 665 SAC. Urine Zn concentration was measured by inductively coupled plasma mass spectrometry with specific gravity adjustment for hydration status. Data were analysed using a linear mixed model with a spatially correlated random effect for between-cluster variation. The effect of time of sample collection (morning or afternoon), and gender (for SAC), on urine Zn concentration were examined. There was spatial dependence in urine Zn concentration between clusters among SAC but not WRA, which indicates that food system or environmental factors can influence urine Zn concentration. Mapping urine Zn concentration could potentially identify areas where the prevalence of Zn deficiency is greater and thus where further sampling or interventions might be targeted. There was no evidence for differences in urine Zn concentration between gender (P = 0.69) or time of sample collection (P = 0.85) in SAC. Urine Zn concentration was greater in afternoon samples for WRA (P = 0.003). Relationships between urine Zn concentration, serum Zn concentration, dietary Zn intake, and potential food systems covariates warrant further study

Estimating the burden of iron deficiency among African children.

BACKGROUND: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. METHODS: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8?years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin <?12??g/L or <?30??g/L in the presence of inflammation in children <?5?years old or <?15??g/L in children ??5?years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. RESULTS: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation <?11% most closely predicted the prevalence of ID according to the regression-correction gold standard. CONCLUSIONS: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa

Prevalence of inherited blood disorders and associations with malaria and anemia in Malawian children

In sub-Saharan Africa, inherited causes of anemia are common, but data are limited regarding the geographical prevalence and coinheritance of these conditions and their overall contributions to childhood anemia. To address these questions in Malawi, we performed a secondary analysis of the 2015-2016 Malawi Micronutrient Survey, a nationally and regionally representative survey that estimated the prevalence of micronutrient deficiencies and evaluated both inherited and noninherited determinants of anemia. Children age 6 to 59 months were sampled from 105 clusters within the 2015-2016 Malawi Demographic Health Survey. Hemoglobin, ferritin, retinol binding protein, malaria, and inflammatory biomarkers were measured from venous blood. Molecular studies were performed using dried blood spots to determine the presence of sickle cell disease or trait, α-thalassemia trait, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 1279 eligible children, 1071 were included in the final analysis. Anemia, iron deficiency, and malaria were common, affecting 30.9%, 21.5%, and 27.8% of the participating children, respectively. α-Thalassemia trait was common (>40% of children demonstrating deletion of 1 [33.1%] or 2 [10.0%] α-globin genes) and associated with higher prevalence of anemia (P < .001). Approximately 20% of males had G6PD deficiency, which was associated with a 1.0 g/dL protection in hemoglobin decline during malaria infection (P = .02). These data document that inherited blood disorders are common and likely play an important role in the prevalence of anemia and malaria in Malawian children

The risk of selenium deficiency in Malawi is large and varies over multiple spatial scales

Selenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3